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Abstract Genetic variants in relevant genes coexisting with MRI lesions in children with drug‐resistant epilepsy (DRE) can negatively influence epilepsy surgery outcomes. Still, presurgical evaluation does not include genetic diagnostics routinely. Here, we report our presurgical evaluation algorithm that includes routine genetic testing. We analyzed retrospectively the data of 68 children with DRE operated at a mean age of 7.8 years (IQR: 8.1 years) at our center. In 49 children, genetic test results were available. We identified 21 gene variants (ACMG III: n = 7, ACMG IV: n = 2, ACMG V: n = 12) in 19 patients (45.2%) in the genes TSC1, TSC2, MECP2, DEPDC5, HUWE1, GRIN1, ASH1I, TRIO, KIF5C, CDON, ANKD11, TGFBR2, ATN1, COL4A1, JAK2, KCNQ2, ATP1A2, and GLI3 by whole‐exome sequencing as well as deletions and duplications by array CGH in six patients. While the results did not change the surgery indication, they supported counseling with respect to postoperative chance of seizure freedom and weaning of antiseizure medication (ASM). The presence of genetic findings leads to the postoperative retention of at least one ASM. In our cohort, the International League against Epilepsy (ILAE) seizure outcome did not differ between patients with and without abnormal genetic findings. However, in the 7/68 patients with an unsatisfactory ILAE seizure outcome IV or V 12 months postsurgery, 2 had an abnormal or suspicious genetic finding as a putative explanation for persisting seizures postsurgery, and 3 had received palliative surgery including one TSC patient. This study highlights the importance of genetic testing in children with DRE to address putative underlying germline variants as genetic epilepsy causes or predisposing factors that guide patient and/or parent counseling on a case‐by‐case with respect to their individual chance of postoperative seizure freedom and ASM weaning. Plain Language Summary Genetic variants in children with drug‐resistant epilepsy (DRE) can negatively influence epilepsy surgery outcomes. However, presurgical evaluation does not include genetic diagnostics routinely. This retrospective study analyzed the genetic testing results of the 68 pediatric patients who received epilepsy surgery in our center. We identified 21 gene variants by whole‐exome sequencing as well as deletions and duplications by array CGH in 6 patients. These results highlight the importance of genetic testing in children with DRE to guide patient and/or parent counseling on a case‐by‐case with respect to their individual chance of postoperative seizure freedom and ASM weaning.

Abstract Although epilepsy surgery is the only curative therapeutic approach for lesional drug‐resistant epilepsy (DRE), there is reluctance to operate on infants due to a fear of complications. A recent meta‐analysis showed that epilepsy surgery in the first 6 months of life can achieve seizure control in about two thirds of children. However, robust data on surgical complications and postoperative cognitive development are lacking. We performed a retrospective multicenter study of infants who underwent epilepsy surgery in the first 6 months of life. 15 infants underwent epilepsy surgery at a median age of 134 days (IQR: 58) at four centers. The most common cause was malformation of cortical development, and 13 patients underwent a hemispherotomy. Two thirds required intraoperative red blood transfusions. Severe intraoperative complications occurred in two patients including death in one infant due to cardiovascular insufficiency. At a median follow‐up of 1.5 years (IQR: 1.8), 57% of patients were seizure‐free. Three patients where reoperated at a later age, resulting in 79% seizure freedom. Anti‐seizure medication could be reduced in two thirds, and all patients improved in their development. Our findings suggest that early epilepsy surgery can result in good seizure control and developmental improvement. However, given the perioperative risks, it should be performed only in specialized centers.

Abstract To evaluate the diagnostic performance of magnetic resonance imaging (MRI) alone in comparison to positron emission tomography/ magnetic resonance imaging (PET/MRI) in patients with meningiomas. 57 patients with a total of 112 meningiomas of the brain were included. PET/MRI, including a fully diagnostic contrast enhanced MRI and PET, were acquired. PET/MRI was used as reference standard. The size and location of meningiomas was recorded. Likelihood-ratio chi-square tests were used to calculate p-values within logistic regression in order to compare different models. A multi-level logistic regression was applied to comply the hierarchical data structure. Multi-level regression adjusts for clustering in data was performed. The majority (n = 103) of meningiomas could be identified based on standard MRI sequences compared to PET/MRI. MRI alone achieved a sensitivity of 95% (95% CI 0.78, 0.99) and specificity of 88% (95% CI 0.58, 0.98). Based on intensity of contrast medium uptake, 97 meningiomas could be diagnosed with intense uptake (93.75%). Sensitivity was lowest with 74% for meningiomas 2cm3 and highest with 100% for meningiomas 0.5–1.0 cm3. Petroclival meningiomas showed lowest sensitivity with 88% compared to sphenoidal meningiomas with 94% and orbital meningiomas with 100%. Specificity of meningioma diagnostic with MRI was high with 100% for sphenoidal and hemispherical-dural meningiomas and meningiomas with 0.5–1.0 and 1.0–2.0 cm3. Overall MRI enables reliable detection of meningiomas compared to PET/MRI. PET/MRI imaging offers highest sensitivity and specificity for small or difficult located meningiomas.

Background: Neonatal drug-resistant epilepsy is often caused by perinatal epileptogenic insults such as stroke, ischemia, hemorrhage, and/or genetic defects. Rapid seizure control is particularly important for cognitive development. Since early surgical intervention and thus a short duration of epilepsy should lead to an optimal developmental outcome, we present our experience with hemispherotomy in an infant at the corrected age of 1 week.Methods: We report successful hemispherotomy for drug-resistant epilepsy in an infant with hemimegalencephaly at a corrected age of 1 week.Results: The infant was diagnosed with drug-resistant lesional epilepsy due to hemimegalencephaly affecting the left hemisphere. Given congruent electroclinical findings, we performed a left vertical parasagittal transventricular hemispherotomy after critical interdisciplinary discussion. No complications occurred during the surgery. Intraoperatively; 118 ml of red blood cells (30 ml/kg) and 80 ml of plasma were transfused. The patient has been seizure-free since discharge without further neurological deficits.Conclusion: We demonstrate that early epilepsy surgery is a safe procedure in very young infants if performed in a specialized center experienced with age-specific surgical conditions and perioperative management. The specific surgical difficulties should be weighed against the risk of life-long developmental drawbacks of ongoing detrimental epilepsy.

Abstract Introduction Cardiovascular disease increases the risk of developing Alzheimer's disease (AD), and growing evidence suggests an involvement of cerebrovascular pathology in AD. Capillary dysfunction, a condition in which capillary flow disturbances rather than arterial blood supply limit brain oxygen extraction, could represent an overlooked vascular contributor to neurodegeneration. We examined whether cortical capillary transit‐time heterogeneity (CTH), an index of capillary dysfunction, is elevated in amyloid‐positive patients with mild cognitive impairment (prodromal AD [pAD]). Methods We performed structural and perfusion weighted MRI in 22 pAD patients and 21 healthy controls. Results We found hypoperfusion, reduced blood volume, and elevated CTH in the parietal and frontal cortices of pAD‐patients compared to controls, while only the precuneus showed focal cortical atrophy. Discussion We propose that microvascular flow disturbances antedate cortical atrophy and may limit local tissue oxygenation in pAD. We speculate that capillary dysfunction contributes to the development of neurodegeneration in AD.

Background and purpose: Patients with head and neck (HN) cancer may benefit from proton therapy due to the potential for sparing of normal tissue. For planning of proton therapy, dual-energy CT (DECT) has been shown to provide superior stopping power ratio (SPR) determination in phantom materials and organic tissue samples, compared to single-energy CT (SECT). However, the benefit of DECT in HN cancer patients has not yet been investigated. This study therefore compared DECT- and SECT-based SPR estimation for HN cancer patients. Materials and methods: Fourteen HN cancer patients were DECT scanned. Eight patients were scanned using a dual source DECT scanner and six were scanned with a conventional SECT scanner by acquiring two consecutive scans. SECT image sets were computed as a weighted summation of the low and high energy DECT image sets. DECT- and SECT-based SPR maps were derived. Water-equivalent path lengths (WEPLs) through the SPR maps were compared in the eight cases with dual source DECT scans. Mean SPR estimates over region-of-interests (ROIs) in the cranium, brain and eyes were analyzed for all patients. Results: A median WEPL difference of 1.9 mm (1.5%) was found across the eight patients. Statistically significant SPR differences were seen for the ROIs in the brain and eyes, with the SPR estimates based on DECT overall lower than for SECT. Conclusions: Clinically relevant WEPL and SPR differences were found between DECT and SECT, which could imply that the accuracy of treatment planning for proton therapy would benefit from DECT-based SPR estimation. Keywords: Proton therapy, Stopping power ratio, Dual-energy CT, Water-equivalent path length, Head and neck cancer

We here report the case of a 2-year-old patient with a primary central nervous system lymphoma of B-cell origin. Due to their past medical history of repeated respiratory tract infections and the marked chemotherapy-associated toxicity and infectious comorbidity, we suspected that the patient also suffered from an inherited immune deficiency disorder. Despite the lack of classical pathognomonic symptoms for ataxia teleangiectasia and missing evidence for a cancer predisposition syndrome in the family, genetic testing identified biallelic germline mutations, including the rare pathogenic variant c.3206delC (p.Pro1069Leufs*2), in the ataxia telangiectasia-mutated (ATM) gene. The case highlights the importance of searching for immune deficiency disorders associated with primary central nervous system lymphoma before treatment initiation and the urgent need to develop novel treatment strategies for cancer patients with underlying immunodeficiency syndromes.

PurposeIn dynamic contrast enhanced (DCE) MRI, separation of signal contributions from perfusion and leakage requires robust estimation of parameters in a pharmacokinetic model. We present and quantify the performance of a method to compute tissue hemodynamic parameters from DCE data using established pharmacokinetic models.MethodsWe propose a Bayesian scheme to obtain perfusion metrics from DCE MRI data. Initial performance is assessed through digital phantoms of the extended Tofts model (ETM) and the two-compartment exchange model (2CXM), comparing the Bayesian scheme to the standard Levenberg-Marquardt (LM) algorithm. Digital phantoms are also invoked to identify limitations in the pharmacokinetic models related to measurement conditions. Using computed maps of the extra vascular volume (ve) from 19 glioma patients, we analyze differences in the number of un-physiological high-intensity ve values for both ETM and 2CXM, using a one-tailed paired t-test assuming un-equal variance.ResultsThe Bayesian parameter estimation scheme demonstrated superior performance over the LM technique in the digital phantom simulations. In addition, we identified limitations in parameter reliability in relation to scan duration for the 2CXM. DCE data for glioma and cervical cancer patients was analyzed with both algorithms and demonstrated improvement in image readability for the Bayesian method. The Bayesian method demonstrated significantly fewer non-physiological high-intensity ve values for the ETM (pConclusionWe have demonstrated substantial improvement of the perceptive quality of pharmacokinetic parameters from advanced compartment models using the Bayesian parameter estimation scheme as compared to the LM technique.

PURPOSE:The purpose of this work is to investigate if the curve-fitting algorithm in Dynamic Contrast Enhanced (DCE) MRI experiments influences the diagnostic quality of calculated parameter maps. MATERIAL AND METHODS:We compared the Levenberg-Marquardt (LM) and a Bayesian method (BM) in DCE data of 42 glioma patients, using two compartmental models (extended Toft's and 2-compartment-exchange model). Logistic regression and an ordinal linear mixed model were used to investigate if the image quality differed between the curve-fitting algorithms and to quantify if image quality was affected for different parameters and algorithms. The diagnostic performance to discriminate between high-grade and low-grade gliomas was compared by applying a Wilcoxon signed-rank test (statistical significance p>0.05). Two neuroradiologists assessed different qualitative imaging features. RESULTS:Parameter maps based on BM, particularly those describing the blood-brain barrier, were superior those based on LM. The image quality was found to be significantly improved (p

Deficient microvascular blood flow control is thought to cause tumor hypoxia and increase resistance to therapy. In glioma patients, we tested whether perfusion-weighted MRI (PWI) based indices of microvascular flow control provide more information on tumor grade and patient outcome than does the established PWI angiogenesis marker, cerebral blood volume (CBV).Seventy-two glioma patients (sixty high-grade, twelve low-grade gliomas) were included. Capillary transit time heterogeneity (CTH) and the coefficient of variation (COV), its ratio to blood mean transit time, provide indices of microvascular flow control and the extent to which oxygen can be extracted by tumor tissue. The ability of these parameters and CBV to differentiate tumor grade were assessed by receiver operating characteristic curves and logistic regression. Their ability to predict time to progression and overall survival was examined by the Cox proportional-hazards regression model, and by survival curves using log-rank tests.The best prediction of grade (AUC = 0.876; p < 0.05) was achieved by combining knowledge of CBV and CTH in the enhancing tumor and peri-focal edema, and patients with glioblastoma multiforme were identified best by CTH (AUC = 0.763; p